Disorders of blood coagulation and thrombosis complicating atherosclerosis are major causes of death and disability. Our objectives in this Resource Grant are: 1) To maintain a breeding colony of well- characterized dogs with genetically-determined bleeding disorders at the Francisco Owen Blood Research Laboratory (FOBRL), University of North Carolina, Chapel Hill; 2) To produce purpose bred-research animals with these bleeding disorders; and 3) To provide specialized support services for research projects using these dogs including canine blood banking and coagulation analyses. These dogs model human hemophilia A, hemophilia B, and von Willebrand disease (vWD) and have been maintained for over 50 years in Chapel Hill largely through support from the NIH. A well-trained support staff at the FOBRL has several years experience in managing these special dogs, maintaining a canine blood bank, developing and performing canine coagulation assays, conducting investigations, and collaborating successfully with investigators worldwide. As a result, research using the dugs from the FOBRL has lead to discoveries that have revolutionized treatment of inherited and acquired bleeding and thrombotic disorders. Many therapeutic agents have moved successfully from the research bench to clinical practice after being conceived of and tested in these dogs. Current research with these large animal models addresses several unmet national needs including the development of new methods of treatment for bleeding and thrombosis, and determination of the acute and chronic sequelae of these new treatments on genetic diseases. As such, these dogs constitute a unique national resource that have been regarded by many investigators as essential for pre-clinical testing of new treatments for the hemophilias, vWD, arterial thrombotic disorders, and hemorrhage. The demand for and use of these hemophilic dogs has nearly doubled during the past two decades. Beginning March 1999, there will be no NIH grant support for the maintenance of this colony making new research using these priceless bleeder drugs very difficult and extensive to initiate. The survival of the FOBRL colony will be jeopardized. The cost of establishing a colony at each investigator's institution is prohibitive. The primary benefit of this grant will be to maintain breeding stock for producing affordable, purpose-bred research animals in a cost-effective manner for the research community. The research animals will be supported by mechanisms that will separate from this Resource Grant. This Resource Grant is essential to ensue the survival of the colony in an established, successful environment.